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Molecular and Cellular Biology, May 2001, p. 3071-3082, Vol. 21, No. 9
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.9.3071-3082.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Negative Regulation of CD4 Gene Expression by a HES-1-c-Myb Complex

Robert D. Allen III,dagger Han K. Kim, Sophia D. Sarafova,Dagger and Gerald Siu*

Department of Microbiology, Columbia University, College of Physicians and Surgeons, New York, New York 10032

Received 24 March 2000/Returned for modification 5 June 2000/Accepted 5 February 2001

Expression of the CD4 gene is tightly controlled throughout thymopoiesis. The downregulation of CD4 gene expression in CD4- CD8- and CD4- CD8+ T lymphocytes is controlled by a transcriptional silencer located in the first intron of the CD4 locus. Here, we determine that the c-Myb transcription factor binds to a functional site in the CD4 silencer. As c-Myb is also required for CD4 promoter function, these data indicate that depending on the context, c-Myb plays both positive and negative roles in the control of CD4 gene expression. Interestingly, a second CD4 silencer-binding factor, HES-1, binds to c-Myb in vivo and induces it to become a transcriptional repressor. We propose that the recruitment of HES-1 and c-Myb to the silencer leads to the formation of a multifactor complex that induces silencer function and repression of CD4 gene expression.

* Corresponding author. Mailing address: Department of Microbiology, Columbia University, College of Physicians and Surgeons, 701 West 168th St., New York, NY 10032. Phone: (212) 305-2743. Fax: (212) 305-8013. E-mail: siu{at}cusiu3.cpmc.columbia.edu.

dagger Present address: Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.

Dagger Present address: Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892-1360.

Molecular and Cellular Biology, May 2001, p. 3071-3082, Vol. 21, No. 9
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.9.3071-3082.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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